Differential and cell-specific expression of calcitonin receptor-like receptor and receptor activity modifying proteins in the human uterus
Open accessAbstract
The calcitonin receptor-like receptor (CRLR) can function as a receptor for either calcitonin gene-related peptide (CGRP) or adrenomedullin (AM), depending upon co-expression with members of a novel family of receptor activity-modifying proteins (RAMP). RAMP1 presents the CRLR at the cell surface as a CGRP/AM receptor. RAMP2- and RAMP3-transported CRLR receptors act as AM-specific receptors. However, it is still unknown if this signalling system operates in vivo. Of particular interest is the uterus, where both peptides and their binding sites are known to be present and where both mitogenic and vasodilatory responses to AM and CGRP have been demonstrated. In this study, we examined whether CRLR and RAMP are co-expressed in the same populations of cells in human uterine tissue. Analysis by in-situ hybridization and immunocytochemistry revealed a heterogeneous and cell type-specific distribution of components of this AM/CGRP signalling system. Adrenomedullin mRNA was expressed and evenly distributed across all cell types. CRLR mRNA was predominantly found in blood vessels. RAMP1 expression was specific to myometrial myocytes and vascular smooth muscle cells in uterine arteries. RAMP2 and RAMP3 mRNA were not detectable by in-situ hybridization. The pattern of differential and cell-specific expression of CRLR and RAMP suggests the involvement of CRLR/RAMP1 in the processes of vasodilation, smooth muscle relaxation and angiogenesis in response to AM and CGRP in the human uterus, but also indicates that other receptors may be implicated.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
NK1R is expressed in human and rodent uterus, as are CRLR and RAMP1.
“NK1R is expressed in human and rodent uterus66–69, so are CRLR and RAMP170.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [70]
Cites
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing
Rosenfeld, M. G., Mermod, J.-J., Amara, S. G., Swanson, L. W., Sawchenko, P. E., Rivier, J., Vale, W. W., & Evans, R. M. (1983) · Nature · doi:10.1038/304129a0 · Cited by 2,302 · see citing works
RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor
McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown, J., Thompson, N., Solari, R., Lee, M. G., & Foord, S. M. (1998) · Nature · doi:10.1038/30666 · Cited by 2,134 · see citing works
Amara, S. G., Jonas, V., Rosenfeld, M. G., Ong, E. S., & Evans, R. M. (1982) · Nature · doi:10.1038/298240a0 · Cited by 2,105 · see citing works
Calcitonin gene-related peptide is a potent vasodilator
Brain, S. D., Williams, T. J., Tippins, J. R., Morris, H. R., & MacIntyre, I. M. (1985) · Nature · doi:10.1038/313054a0 · Cited by 2,086 · see citing works
Barnes, W. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.6.2216 · Cited by 1,041 · see citing works
Adrenomedullin, a Multifunctional Regulatory Peptide*
Hinson, J. P., Kapas, S., & Smith, D. M. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.2.0396 · Cited by 759 · see citing works
Self-citationCloning and Characterization of cDNA Encoding a Precursor for Human Adrenomedullin
Kitamura, K., Sakata, J., Kangawa, K., Kojima, M., Matsuo, H., & Eto, T. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1881 · Cited by 604 · see citing works
van Rossum, D., Hanisch, U., & Quirion, R. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00023-1 · Cited by 512 · see citing works
Dennis, T., Fournier, A., Cadieux, A., Pomerleau, F., JOLICOEUR, F. B., St-Pierre, S. A., & Quirion, R. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12587-1 · Cited by 327 · see citing works
A cDNA Encoding the Calcitonin Gene-related Peptide Type 1 Receptor
Aiyar, N. V., Rand, K., Elshourbagy, N. A., Zeng, Z., Adamou, J. E., Bergsma, D. J., & Li, Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.19.11325 · Cited by 320 · see citing works
Adrenomedullin, a Multifunctional Regulatory Peptide
Hinson, J. P. (2000) · Endocrine Reviews · doi:10.1210/er.21.2.138 · Cited by 256 · see citing works
Dennis, T., Fournier, A., St-Pierre, S. A., & Quirion, R. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20868-0 · Cited by 225 · see citing works
Shindo, T., Kurihara, H., Maemura, K., Kurihara, Y., Kuwaki, T., Izumida, T., Minamino, N., Ju, K., Morita, H., Oh-hashi, Y., et al. (2000) · Circulation · doi:10.1161/01.cir.101.19.2309 · Cited by 166 · see citing works
Increased Blood Pressure in α-Calcitonin Gene–Related Peptide/Calcitonin Gene Knockout Mice
Gangula, P. R., Zhao, H., Supowit, S. C., Wimalawansa, S. J., DiPette, D. J., Westlund, K. N., Gagel, R. F., & Yallampalli, C. (2000) · Hypertension · doi:10.1161/01.hyp.35.1.470 · Cited by 145 · see citing works
A New Calcitonin-Receptor-like Sequence in Rat Pulmonary Blood Vessels
Njuki, F., Nicholl, C. G., Howard, A., Mak, J. C. W., Barnes, P. J., Girgis, S. I., & Legon, S. (1993) · Clinical Science · doi:10.1042/cs0850385 · Cited by 142 · see citing works
Zhao, Y., Hague, S. J., Manek, S., et al. (1998) · Oncogene · doi:10.1038/sj.onc.1201768 · Cited by 134 · see citing works
Kamitani, S., Asakawa, M., Shimekake, Y., Kuwasako, K., Nakahara, K., & Sakata, T. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00358-0 · Cited by 128 · see citing works
Chakravarty, P., Suthar, T. P., Coppock, H. A., Nicholl, C., Bloom, S. R., Legon, S., & Smith, D. M. (2000) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0702975 · Cited by 122 · see citing works
Self-citationMonoclonal antibodies that recognize discrete forms of tubulin.
Gozes, I., & Barnstable, C. J. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.8.2579 · Cited by 115 · see citing works
Nagae, T., Mukoyama, M., Sugawara, A., Mori, K., Yahata, K., Kasahara, M., Suganami, T., Makino, H., Fujinaga, Y., Yoshioka, T., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2390 · Cited by 114 · see citing works
Novel Sites of Adrenomedullin Gene Expression in Mouse and Rat Tissues1
Cameron, V. A., & Fleming, A. M. (1998) · Endocrinology · doi:10.1210/endo.139.5.5965 · Cited by 105 · see citing works
Hague, S. J., Zhang, L., Oehler, M. K., Manek, S., MacKenzie, I. Z., Bicknell, R., & REES, M. C. P. (2000) · PubMed · Cited by 97 · see citing works
Self-citationAdrenomedullin is an autocrine regulator of endothelial growth in human endometrium
Nikitenko, L. L. (2000) · Molecular Human Reproduction · doi:10.1093/molehr/6.9.811 · Cited by 89 · see citing works
Self-citationEffects of a synthetic rat adrenomedullin on regional hemodynamics in rats
He, H., Bessho, H., Fujisawa, Y., Horiuchi, K., Tomohiro, A., Kita, T., Aki, Y., Kimura, S., Tamaki, T., & Abe, Y. (1995) · European Journal of Pharmacology · doi:10.1016/0014-2999(94)00683-x · Cited by 87 · see citing works
Calcitonin gene-related peptide inhibits spontaneous contractions in human uterus and fallopian tube
Samuelson, U., Dalsgaard, C., Lundberg, J. M., & Hökfelt, T. G. M. (1985) · Neuroscience Letters · doi:10.1016/0304-3940(85)90359-3 · Cited by 83 · see citing works
Husmann, K., Sexton, P. M., Fischer, J. A., & Born, W. (2000) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(00)00212-4 · Cited by 80 · see citing works
Shew, R. L., Papka, R. E., & McNeill, D. L. (1991) · Peptides · doi:10.1016/0196-9781(91)90107-z · Cited by 74 · see citing works
Muff, R., Leuthäuser, K., Bühlmann, N., Foord, S. M., Fischer, J. A., & Born, W. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)01587-7 · Cited by 73 · see citing works
Upton, P. D., Austin, C., Taylor, G. M., Nandha, K. A., Clark, A., Ghatei, M. A., Bloom, S. R., & Smith, D. M. (1997) · Endocrinology · doi:10.1210/endo.138.6.5186 · Cited by 73 · see citing works
Self-citationMammalian cell transformation and aneuploidy induced by five bisphenols
Tsutsui, T., Tamura, Y., Suzuki, A., Hirose, Y., Kobayashi, M., Nishimura, H., Metzler, M., & Barrett, J. C. (2000) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(20000415)86:2 · Cited by 70 · see citing works
Oliver, K. R., Wainwright, A., HEAVENS, R. P., Hill, R. G., & SIRINATHSINGHJI, D. J. S. (1998) · Molecular Brain Research · doi:10.1016/s0169-328x(98)00052-7 · Cited by 66 · see citing works
Calcitonin gene-related peptide-α receptor binding sites in the gastrointestinal tract
Gates, T. S., Zimmerman, R. P., Mantyh, C. R., et al. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90439-9 · Cited by 63 · see citing works
Morrish, D. W., Linetsky, E., Bhardwaj, D., Li, H., Dakour, J., Marsha, R. G., Paterson, M. C., & Godbout, R. (1996) · Placenta · doi:10.1016/s0143-4004(96)90025-9 · Cited by 60 · see citing works
Adrenomedullin and atrial natriuretic peptide concentrations in normal pregnancy and pre-eclampsia
Minegishi, T. (1999) · Molecular Human Reproduction · doi:10.1093/molehr/5.8.767 · Cited by 55 · see citing works
Trembleau, A., & Bloom, F. E. (1995) · Journal of Histochemistry & Cytochemistry · doi:10.1177/43.8.7622844 · Cited by 52 · see citing works
Kobayashi, K., Kubota, T., Aso, T., et al. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1420683 · Cited by 52 · see citing works
Novel Sites of Adrenomedullin Gene Expression in Mouse and Rat Tissues
Cameron, V. A. (1998) · Endocrinology · doi:10.1210/en.139.5.2253 · Cited by 47 · see citing works
Receptors for calcitonin, calcitonin gene related peptide, amylin, and adrenomedullin
Muff, R., Born, W., & Fischer, J. A. (1995) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y95-133 · Cited by 40 · see citing works
Shew, R. L., Papka, R. E., & McNeill, D. L. (1992) · Peptides · doi:10.1016/0196-9781(92)90108-f · Cited by 33 · see citing works
H�pp�la, O., & Łakomy, M. (1989) · Histochemistry and Cell Biology · doi:10.1007/bf00500920 · Cited by 32 · see citing works
Yallampalli, C., Gangula, P. R., Kondapaka, S. B., et al. (1999) · Biology of Reproduction · doi:10.1095/biolreprod61.4.1023 · Cited by 32 · see citing works
Papka, R. E., Thompson, B. D., & Schmidt, H. H. H. W. (1996) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(96)00003-3 · Cited by 32 · see citing works
Activation of Adenylyl Cyclase in Human Myometrial Smooth Muscle Cells by Neuropeptides1
Casey, M. L., Smith, J. M., Alsabrook, G., et al. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.9.4244 · Cited by 31 · see citing works
Bodelsson, G., & Stjernquist, M. (1992) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a137823 · Cited by 29 · see citing works
Moriyama, T., Otani, T., & Maruo, T. (2000) · European Journal of Endocrinology · doi:10.1530/eje.0.1420671 · Cited by 27 · see citing works
Expression of adrenomedullin in the human corpus luteum
Abe, K., Minegishi, T., Ibuki, Y., et al. (2000) · Fertility and Sterility · doi:10.1016/s0015-0282(00)00585-9 · Cited by 26 · see citing works
Possible physiologic role of calcitonin gene-related peptide in the human uterine artery
Nelson, S. H., Steinsland, O. S., & Suresh, S. (1993) · American Journal of Obstetrics and Gynecology · doi:10.1016/0002-9378(93)90503-b · Cited by 25 · see citing works
Flühmann, B., Lauber, M., LICHTENSTEIGER, W., Fischer, J. A., & Born, W. (1997) · Brain Research · doi:10.1016/s0006-8993(97)81702-7 · Cited by 25 · see citing works
Activation of Adenylyl Cyclase in Human Myometrial Smooth Muscle Cells by Neuropeptides
Casey, M. L. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.82.9.3087 · Cited by 25 · see citing works
Expression of adrenomedullin in the endometrium of the human uterus
Michishita, M. (1999) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(98)00357-3 · Cited by 23 · see citing works
Nelson, S. H., Suresh, S., Dehring, D. J., et al. (1993) · European Journal of Pharmacology · doi:10.1016/0014-2999(93)90249-h · Cited by 19 · see citing works
Effects of Human Calcitonin Gene-Related Peptide and Substance P on Human Intracervical Arteries
Hansen, V., Schifter, S. O. R., Allen, J., et al. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000293795 · Cited by 10 · see citing works
Reinecke, M., Gauwerky, J. F. H., & Schneider, K. (1989) · Archives of Gynecology and Obstetrics · doi:10.1007/bf02417342 · Cited by 10 · see citing works
Expression of Adrenomedullin in the Endometrium of the Human Uterus
MICHISHITA, M., Minegishi, T., ABE, K., et al. (1999) · Obstetrics and Gynecology · doi:10.1097/00006250-199901000-00014 · Cited by 7 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
- Authors
- Nikitenko, L. L., Brown, N. S., Smith, D. M., MacKenzie, I. Z., Bicknell, R., & Rees, M. C. P.
- Affiliations
- John Radcliffe Hospital (GB)
- Venue
- MHR: Basic science of reproductive medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-07
- Volume
- 7
- Issue
- 7
- Pages
- 655-664
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- OpenAlex
- W2107516088
- Cited by
- 49
- References
- 56
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 3 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.35
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Molecular Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- calcitonin receptor-like receptor, receptor activity-modifying proteins, RAMP1, RAMP2, RAMP3, adrenomedullin, calcitonin gene-related peptide, human uterus, myometrium, uterine artery, vascular smooth muscle cells, cell type-specific gene expression, vasodilation, smooth muscle relaxation, angiogenesis
- MeSH terms
- Adult, Endometrium, Female, Humans, Immunoenzyme Techniques, Membrane Proteins, Middle Aged, Myometrium, Peptides, RNA, Messenger, Uterus, Calcitonin Gene-Related Peptide, Gene Expression, In Situ Hybridization, Receptors, Calcitonin, Intracellular Signaling Peptides and Proteins, Adrenomedullin, Receptor Activity-Modifying Proteins, Receptor Activity-Modifying Protein 1, Receptor Activity-Modifying Protein 2, Receptor Activity-Modifying Protein 3, Calcitonin Receptor-Like Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
